Antemortem Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy in a Patient with Recurrent Breast Cancer: An Autopsy Case Report.

OBJECTIVE: Herein, we report a case of a patient with recurrent breast cancer who was diagnosed antemortem with pulmonary tumor thrombotic microangiopathy (PTTM) using wedge aspiration cytology of the pulmonary artery after breast cancer surgery. CASE SUMMARY: The patient was a 50-year-old woman who underwent mastectomy and axillary lymph node dissection for stage IIIA (T3N2M0) triple-negative left breast cancer. Postoperative follow-up was performed with radiotherapy and anticancer chemotherapy. Seventeen months after the surgery, the patient was hospitalized for right heart failure and diagnosed with pulmonary arterial hypertension. The patient was diagnosed with PTTM following the detection of malignant cells in the pulmonary artery using wedge aspiration cytology. Anti-pulmonary hypertension therapy was administered; however, the patient did not respond and died 26 days after admission. Autopsy revealed multiple microscopic tumor emboli in the pulmonary artery. In portions of the pulmonary artery without embolization, fibro-cellular intimal hyperplasia and stenosis were observed. Tumor embolism was expressed for CK7+/CK20-, consistent with the primary breast cancer. DISCUSSION: Since the primary pathophysiology of PTTM entails narrowing due to fibro-cellular intimal hyperplasia rather than multiple tumor thrombi, the efficacy of chemotherapy combined with vasodilators is discussed.

Students' Input on Preparing a Weekly Calendar of Individual Students in the Breast Surgery Clinical Clerkship.

Background; Until 2018, the Breast and Endocrine surgery had no student calendar. A questionnaire survey was conducted on how students felt by creating a weekly schedule of individual students from 2019. METHOD: 6th-year elective courses, targeted at students who selected Breast and Endocrine surgery clinical clerkship. The schedule clarifies the contents of the training as follows; outpatient visits, small group study (preparation for graduation and national exams including mammography reading), simulator training, and surgery. The questionnaire adopted an anonymous five-point evaluation method (5; I think very much; 4; Somewhat I think; 3; Normal; 2; Somewhat I don't think; 1; I don't think), and provided a free text box. The following seven questions were asked; A. I was able to send a good training, B. I was useful for studying national and graduation exams, C. Time constraints were appropriate, D. I could fully experience surgery, E. Appropriately experienced outpatients, F. Assignments (presented at conference) appropriate, G. I was interested in Breast and Endocrine surgery. RESULTS: Average values were A. 4.7, B. 4.9, C. 4.6, D. 4.9, E. 4.8, F. 4.7, G. 4.7. However, C and F received low ratings of 1 and 2. In the free text box, there were favorable opinions such as the fact that it was good to prepare for the national examination and that reading mammography was helpful. Conversely, there were some negative opinions, such as a time spent outpatient was too long, a difference in enthusiasm among the instructors, and a hope to see more at the first visit and to cope with the procedure. DISCUSSION: Preparing a weekly calendar of individual students generally yielded satisfactory results, but also highlighted the potential for future improvements in clinical clerkship.

Myxofibrosarcoma that Developed Rapidly in the Breast of an Elderly Man and Recurred Early after Surgery: A Case Report.

BACKGROUND: Myxofibrosarcoma is a rare disease occurring subcutaneously in the limbs. We report a case of a rapidly growing myxofibrosarcoma in the breast of an elderly man that recurred early after surgery. CASE PRESENTATION: A 73-year-old man presented with a breast mass. Physical findings showed a large tumor in the right breast, and malignancy was suspected on ultrasonography. Computed tomography (CT) revealed tumor invasion into the pectoralis major and pectoralis minor muscles. Positron emission tomography/CT showed no abnormality in other organs. Needle biopsy results excluded breast cancer but did not provide a definitive diagnosis. However, the tumor grew rapidly before further results were available, so emergency mastectomy was performed. The final pathological diagnosis was high-grade myxofibrosarcoma. Postoperative radiotherapy was started because of remnant tumor. The wound became worsened and swollen, and needle biopsy 10 days after the start of therapy indicated recurrence. Radical resection and thoracoplasty were performed. Postoperative pathological specimens showed no residual tumor. Radical radiation therapy was resumed. The patient has shown no recurrence after an year. CONCLUSIONS: It is important to consult a soft tissue oncologist for tumors in the breast and perform appropriate examination and treatment if soft tissue tumors cannot be ruled out.

A Case of Unknown Primary Cancer with a Tumor Formed in the Retroperitoneum: A Case Report.

BACKGROUND: Cancer of unknown primari (CUP) are said to account for 2% of all carcinomas. Here we report a rare case of CUP confined to the retroperitoneum. CASE PRESENTATION: A 51-year-old man consulted a nearby physician for back pain. The malignant tumor could not be denied by MRI, and she was referred to our hospital. CT and MRI revealed uneven enhanced tumor structures protruding into the L2/3 disc. Part of the tumor was continuous with the left iliopsoas muscle. A CT-guided needle biopsy was performed. Histologically, the sheet-like proliferation of atypical cells was observed. Immunohistochemistry showed that atypical cells were positive for cytokeratin AE1&3, CK7, CD10, GATA3, glypican 3, Hep Par 1, carbonic anhydrase 9 (focal), and vimentin (focal) but negative for CK20, CD56, chromogranin A, synaptophysin, TTF1, HMB45, melan A, and PSA. The pathological diagnosis was poorly differentiated carcinoma. However, it was difficult to determine the primary site from the pathological findings. Positron emission tomography (PET) scan showed no distant metastases. He was diagnosed as poorly differentiated cancer localized to the lumbar spine from the retroperitoneum. Paclitaxel plus carboplatin (TC) was started. After completing 3 kr of TC, she was hospitalized urgently due to worsening lumbago. CT and MRI at admission showed an increase in the main lesion and exacerbation of bone invasion. Radiation therapy was given for curative purposes. Eventually, he died seven months after visiting our hospital and five months after starting TC therapy. CONCLUSIONS: CUP has various disease states, and it is necessary to finish the examination immediately and shift to treatment. More effective treatment including immune checkpoint inhibitor for CUP is needed in the future.

Taste alterations in patients with breast cancer following chemotherapy: a cohort study.

BACKGROUND: Chemotherapy-induced taste and smell alterations in cancer patients are associated with multiple adverse effects, namely, malnutrition, weight loss, and a diminished quality of life. The aim of this prospective study was to identify the incidence of taste alterations following epirubicin and cyclophosphamide (EC) chemotherapy in patients with breast cancer without previous history of cancer or chemotherapy. METHODS: Forty-one patients undergoing EC chemotherapy for breast cancer at Tokai University Hospital were included. A subjective (questionnaire) and an objective (filter paper disk method) assessment for 5 basic tastes were administered on day 4 post-chemotherapy and immediately before the subsequent cycle of chemotherapy for each cycle, in addition to an olfactory evaluation and oral examination. The correlation between subjective and objective taste alterations and factors influencing these alterations were analyzed by statistical means. RESULTS: The mean incidence of subjective taste alteration on the 4th day after chemotherapy was 53%. In each of the 4 cycles, taste alterations decreased to about 9.0% immediately before the next cycle. A significant correlation between subjective and objective assessments was seen only for salty taste, suggesting important differences in subjective versus objective assessment outcomes. A multivariate analysis indicated that age and body surface area influenced taste alterations. CONCLUSIONS: EC chemotherapy induced taste alterations in more than 50% of patients, which decreased to less than 10% immediately before the next chemotherapy cycle. A combination of objective and subjective assessments is essential to evaluate taste alterations induced by EC chemotherapy. These could be used in routine clinical practice.

[Two Cases of Pneumocystis Pneumonia during Adjuvant Chemotherapy for Breast Cancer].

In recent years, human immunodeficiency virus(HIV)-negative Pneumocystis pneumonia(PCP)onset has been occasionally seen in breast cancer. In particular, dose-dense epirubicin and cyclophosphamide(EC: ddEC)therapy, in which EC is administered every 2 weeks, has been generally used in clinical practice for early stage breast cancers. PCP may develop before and during postoperative chemotherapy. We report the cases of 2 patients who developed PCP during postoperative adjuvant chemotherapy. Case 1: A 62-year-old woman, who underwent postoperative EC therapy, developed PCP during the 4th EC cycle. During EC therapy, steroids(prednisolone[PSL])were administered at an average dose of 11.4mg/day, and the number of lymphocytes at the initiation of the 4th EC cycle was 516/mL. Case 2: After receiving 4 cycles of postoperative ddEC, a 27-year-old woman developed PCP after 1 cycle of docetaxel(DTX)administration. During ddEC therapy, PSL was administered at a dose of 17.14mg/day, and the number of lymphocytes at DTX administration was 311/mL. The onset of PCP is presumed to be related to the steroid dose administered and the number of lymphocytes. Therefore, determining effective indicators in patients at a high risk of PCP onset is important.

Rare Finding of Bilateral Pseudoangiomatous Stromal Hyperplasia of the Breast: A Case Report.

A 49-year-old woman, with a medical history of rheumatism, was admitted to our hospital with chief complaints of bilateral enlargement and redness of breasts. She underwent weekly breast examinations. Mammography findings were reported as category 3 for both breasts. Breast ultrasonography, magnetic resonance imaging, and chest contrast computed tomography revealed a massive tumor in the left BD region, however, there were no findings for suspected malignancy. Needle biopsy did not yield histologically malignant cells in both breasts. Mammary interstitium was edematous, and capillary-like slit structures were observed. The stroma stained with alcian blue and destained with hyaluronidase treatment. Since the stroma tested positive for vimentin, calponin, and CD34 and negative for CD31, the patient was diagnosed as (PASH). Because both breasts had similar diagnosis based on histopathologic findings, bilateral mastectomy was performed. Details about the origin of bilateral PASH are unknown but it may be related to the development of rheumatoid arthritis. Additionally, systemic autoimmune diseases like rheumatism may be the reason for repeated contraction and enlargement of PASH.

Distinction of IgG4-related mastitis from breast cancer: a case report.

BACKGROUND: Immunoglobulin (Ig) G4-related sclerosing disease is a pathological concept proposed in Japan during the early 2000s. This lesion-forming disease may exhibit characteristics of a systemic disease but often affects a single organ. To date, IgG4-related sclerosing disease in the mammary gland, or IgG4-related mastitis (IgG4-RM), has rarely been reported. CASE PRESENTATION: Here, we describe the case of a female patient who was admitted to our hospital with the main complaints of left breast and axillary lymphadenopathy. A careful diagnostic imaging examination led to an initial suspicion of breast cancer. However, a needle biopsy led to a diagnosis of IgG4-RM. Subsequently, the patient was successfully treated with predonin. CONCLUSIONS: The treatment requirements for breast cancer and IgG4-RM differ considerably. This is a good example of a case wherein unnecessary surgical treatment, which is indicated for breast cancer, was avoided by needle biopsy. Accordingly, the patient was appropriately treated with steroids following a correct diagnosis.

Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists.

BACKGROUND: Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown. METHODS: We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist's scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist's scoring for all patients (κ 0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (p < 0.001) and obtained using image analysis (p = 0.031). CONCLUSIONS: The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.

B-cell populations are expanded in breast cancer patients compared with healthy controls.

BACKGROUND: Historically, humoral immunity was considered unimportant in anti-tumor immunity, and the differentiation and anti-tumor activity of B cells in breast cancer are poorly understood. However, it was recently discovered that B cells participate in tumor immunity through both antibody production and immunosuppressive mechanisms. We analyzed the expression of B-cell differentiation markers in detail using fluorescence-activated cell sorting to investigate the relationship between B-cell subsets and breast cancer etiology. METHODS: Blood samples were taken from breast cancer patients and healthy donors, and peripheral blood mononuclear cells were collected. B cells at various stages of differentiation were identified by the expression of combinations of the cell surface markers CD5, CD19, CD21, CD24, CD27, CD38, CD45, and IgD. Statistical analysis of the proportions of each B-cell subtype in the different patient groups was then performed. RESULTS: Twenty-seven breast cancer patients and 12 controls were considered. The proportion of total B cells was significantly higher in cancer patients than in controls (11.51 ± 2.059 vs 8.905 ± 0.379%, respectively; p = 0.001). Breast cancer patients were then classified as High-B or Low-B for further analysis. A significantly higher proportion of memory B cells was found in the High-B group than in the Low-B or control groups (p = 0.003 and p = 0.043, respectively). CONCLUSIONS: Breast cancer patients generally have a higher proportion of B cells than healthy controls, but this is highly variable. Analysis of the major B-cell surface markers indicates that memory B cells in particular are significantly expanded, or more robust, in breast cancer patients.

Pyoderma Gangrenosum after Breast Mastectomy and Primary Rectus Abdominis Flap Reconstruction.

Pyoderma gangrenosum is an intractable disease of unknown cause involving recurrent ulcerative lesions on the skin, and may accompany ulcerative colitis, rheumatoid arthritis, leukemia, systemic lupus erythematosus, and other conditions. Here, we report a rare case of pyoderma gangrenosum in the thoracic abdomen following post-mastectomy reconstructive surgery. A 39-year-old presented at the hospital with a complaint of left papilla erosion. Skin biopsy at the site revealed invasive skin cancer, with Paget-like progression in the cancerous nipple and suspected malignancy of skin appendages. After partial mastectomy including the areola, invasive ductal breast carcinoma was diagnosed. The patient underwent a subsequent full mastectomy with simultaneous sentinel lymph node biopsy and primary breast reconstructive surgery using a rectus abdominis myocutaneous flap. Two weeks post-surgery, healing of the abdominal surgical wound was found to be delayed, and suture abscess was suspected. Despite localized treatment, an ulcerative lesion developed in the thoracic region, and pyoderma gangrenosum was diagnosed following skin biopsy. After the introduction of steroid pulse therapy, no progression of the lesion was observed. This report describes the disease characteristics, diagnosis, and treatment of post-surgical pyoderma gangrenosum and discusses the case in the context of previous literature.

Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients.

The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2+ , n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8+ and CD4+ T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2+ and TN breast cancers have a lower percentage of TILs and CD8+ and CD4+ T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.

Diagnostic performance of (18)F-fluorodeoxyglucose PET/CT and bone scintigraphy in breast cancer patients with suspected bone metastasis.

BACKGROUND: We prospectively compared the diagnostic accuracies of PET/CT and BS in patients with suspected bone metastases from breast cancer. METHODS: This single-institution prospective study included consecutive patients with suspected bone metastases from biopsy-proven breast cancer seen at Tokai University Hospital between September 2011 and March 2014. Inclusion criteria included suspicions for bone metastases (bone pain, elevated alkaline phosphatase, elevated tumor markers, or suspected bone metastases by BS). Two nuclear medicine physicians evaluated PET/CT and BS images. RESULTS: Thirty patients were initially enrolled in this study. Two were excluded from the analyses because they declined to undergo imaging during follow-up. PET/CT successfully detected bone metastases in all 10 patients finally diagnosed with the condition, whereas BS identified 2. The two methods were not highly concordant in detecting osseous metastases. In 19 of 28 paired studies (68 %), 2 (10 %) were positive for metastasis, and 17 (90 %) were negative. Nine occurrences (32 %) were discordant; of these, 2 were PET/CT positive and BS negative; 5 were PET/CT positive and BS equivocal; one was PET/CT negative and BS equivocal, and one was PET/CT equivocal and BS negative. CONCLUSIONS: Our results indicated that PET/CT was superior to BS for the diagnosis of bone metastases. On the basis of the results of previous studies as well as ours, PET/CT could replace BS as the initial modality to detect bone metastases in patients suspected for the condition.

Prognostic significance of the Ki67 scoring categories in breast cancer subgroups.

BACKGROUND: Immunohistochemical (IHC) expression of Ki67 has a prognostic and predictive value for breast cancer, and the IHC Ki67 labeling index is estimated by counting the number of positive and negative cells. It has not been clarified whether IHC Ki67 estimated using a semiquantitative scoring system has a prognostic value. We aimed to estimate the usefulness of scoring categories of IHC Ki67 as a prognostic factor for breast cancer subgroups. PATIENTS AND METHODS: We retrospectively identified patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000 and December 31, 2010. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of the 1331 primary breast cancer patients included in the study, In patients with estrogen receptor (ER)-positive and HER2-negative tumors (n = 971), high and intermediate Ki67 scores were associated with poorer relapse-free survival than low Ki67 scores (P < .001 and P = .002, respectively). Furthermore, in the multivariate analyses of this subgroup, progression-free survival (PFS) was significantly longer in patients with low Ki67 scores than in patients with high Ki67 scores (hazard ratio, 0.387; 95% confidence interval, 0.233-0.643; P < .001). In the multivariate analyses, the Ki67 score was not significantly associated with PFS in the ER-positive and HER2-positive, ER-negative and HER2-positive, or ER-negative and HER2-negative subgroups. CONCLUSION: Our data demonstrated that low, intermediate, and high Ki67 scores have a prognostic value in breast cancer patients with ER-positive and HER2-negative tumors.

Feasibility and pharmacokinetics of combined therapy with S-1 and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic or recurrent breast cancer.

BACKGROUND: To clarify the tolerance and pharmacokinetics of combined therapy with S-1 and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic or recurrent breast cancer. METHODS: From January 2008 through to September 2009, combined therapy with S-1 and trastuzumab was given to 7 patients with HER2-positive metastatic or recurrent breast cancer. The incidence of adverse events and the pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil in plasma were studied. RESULTS: One patient had grade 3 leukopenia, and another had a grade 3 elevation of alanine aminotransferase. All other adverse events were grade 2 or lower. The combination of S-1 and trastuzumab did not cause any new adverse events. The incidence of adverse events was similar to those associated with S-1 alone. The median number of treatment cycles was 11. The pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil after treatment with S-1 plus trastuzumab did not markedly differ from those after S-1 alone. CONCLUSIONS: Combined therapy with S-1 and trastuzumab did not cause any new adverse events, administration continuity was good, and the therapy was well tolerated.

Trastuzumab and chemotherapy after the treatment failure of lapatinib for HER2-positive metastatic breast cancer.

We describe a patient with human epidermal growth factor receptor type 2 (HER2/c-erbB-2)-positive metastatic breast cancer who survived for approximately 6 years after the initiation of combination therapy with trastuzumab and varying types of chemotherapeutic agents. The patient was a 48-year-old postmenopausal female who underwent partial mastectomy with axillary node dissection for cancer of the right breast in March 1994. She developed lung metastases 2 years thereafter, but survived free of relapse for 8 years following chemotherapy and pulmonary lobectomy. The patient failed to respond to lapatinib, a HER1 (EGFR)/HER2 tyrosine kinase inhibitor, received during the course of her treatment but then again responded to subsequently administered trastuzumab. Primary treatment with trastuzumab and paclitaxel was initiated in April 2004 when the patient developed hepatic metastases 8 years after undergoing surgery for lung metastases. Long-term combination therapy with continued trastuzumab and a variety of chemotherapeutic agents was administered for 6 years without any significant adverse events. We discuss the treatment strategies for HER2-positive breast cancer and the role of lapatinib, a recently approved anticancer drug.